Genetic polymorphism within the leishmania donovani complex: correlation with geographic origin

Random amplified polymorphic DNA (RAPD) was used to detect intraspecific diversity for the Leishmania donovani complex. Fifty-two decameric to 21-meric primers of arbitrary sequence were applied to 15 strains that belong to nine zymodemes. Strains belonging to the species L. major and L. tropica were used as outgroups. A total of 902 amplicons generated by RAPD were scored. Most primers produced species-specific profiles, only 0.6% amplicons were shared by all species, while 4.3% amplicons were common for all 15 strains of the L. donovani complex. Well-supported trees have been constructed, which show a rather strong correlation between the genetic polymorphism of studied strains and their geographic origin. In all obtained trees, L. infantum was paraphyletic. The RAPD profiles suggest that MON-30 belongs to L. donovani. Moreover, the genetic distance between the L. archibaldi strain and other leishmanias does not warrant existence of a separate species.     

Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis

In a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism (46C-->T) in the F12 locus jointly influences variability of plasma (Factor XII) FXII levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the 46C-->T polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls. We measured FXII levels and genotyped the 46C-->T polymorphism, as well as a number of classical risk factors for thrombotic disease.We confirmed that individuals with different genotypes for this polymorphism showed significant differences in their FXII levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of thrombosis (adjusted OR of 4.82; 95% CI 1.5-15.6), suggesting that the polymorphism itself is an independent risk factor for venous thromboembolism. This study confirms that the 46C-->T polymorphism is a genetic risk factor for venous thrombosis in the Spanish population. In addition, our results confirm that a genome-wide scan coupled with a classical case-control association study is an extremely valuable approach to identify DNA variants that affect complex diseases.     

Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice

The role of alpha-synuclein (alpha-Syn) has recently received considerable attention because it seems to play a role in Parkinson's disease (PD). Missense mutations in the alpha-Syn gene were found in autosomal dominant PD and alpha-Syn was shown to be a major constituent of protein aggregates in sporadic PD and other synucleinopathies. Under normal conditions, alpha-Syn protein is found exclusively in synaptic terminals. However, the potential participation of alpha-synuclein in maintaining and regulating synaptic efficacy is unknown. We have investigated the excitatory synaptic modulation of alpha-synuclein in CA1 pyramidal neurons, using the in vitro hippocampal slice technique. The 4-aminopyridine-induced increase of both spontaneous excitatory postsynaptic current (EPSC) frequency and amplitude was significantly higher in alpha-Syn wild-type than knockout mice, whereas basal spontaneous EPSC frequency and amplitude was similar in both animals. As the spontaneous synaptic activity was abolished by tetrodotoxin, which indicates that it was a result of action potential-mediated transmitter release from presynaptic terminals, spontaneous EPSC changes observed in alpha-Syn knockout mice suggest that these animals present a modification of synaptic transmission with a presynaptic origin. Presynaptic depression of evoked EPSCs by hypoxia or adenosine was significantly larger in alpha-Syn knockout than in wild-type mice, further supporting the hypothesis of regulation of synaptic transmission by alpha-Syn. Together, these observations indicate that the loss of alpha-Syn reduces synaptic efficacy when the probability of transmitter release is modified. We conclude that alpha-Syn might have important actions on the maintenance of the functional integrity of synaptic transmission and its regulation in hippocampus.     

Using conjoint analysis to assess depression treatment preferences among low-income Latinos

The authors examined the feasibility of conjoint analysis for measuring the depression treatment preferences of low-income, low-literacy Latino primary care patients. Forty-two patients with depression (58 percent of those eligible for the study) completed a survey about preferences for treatment and strategies to reduce barriers to care. They preferred combined counseling and medication to either approach alone and preferred individual over group treatment but did not show a significant preference for treatment setting. The odds of treatment acceptance were increased by the availability of telephone appointments, bus passes, and help with making appointments. Although further validation is required, conjoint analysis appears to be feasible for assessing preferences regarding depression treatment in this underserved population.     

Propofol in the management of postictal delirium with clozapine-electroconvulsive therapy combination

Postictal delirium is an acute confusional state occurring during the immediate postictal phase in patients receiving electroconvulsive therapy that is characterized by motor agitation, disorientation, clouded consciousness, repetitive stereotyped movements, and poor response to commands. A schizophrenic patient with severe and recurrent postictal delirium is described. The possible role of the clozapine-electroconvulsive therapy combination in the occurrence of postictal delirium is discussed. Several management strategies were tried, with various degrees of success. Propofol proved to be effective in preventing agitation when used as induction agent or when administered at seizure end. However, propofol could not prevent a delirious state when only administered after the first signs of motor restlessness had emerged.     

Endovascular treatment of cerebrovascular disease

PURPOSE OF REVIEW: This review summarizes recent advances in endovascular therapy for cerebrovascular disease. RECENT FINDINGS: For ruptured aneurysms, the only large, randomized, controlled trial comparing surgical and endovascular treatment (the International Subarachnoid Aneurysm Trial) resulted in a significant reduction in death or dependency at 1 year, compared with surgery, providing sound evidence that coiling should be the treatment of first choice. Data from the International Study of Unruptured Intracranial Aneurysms demonstrated that treatment of unruptured anterior circulation aneurysms of under 7 mm with no history of subarachnoid hemorrhage is not justified. Embolization of arteriovenous malformations, as sole therapy, is curative only in a small percentage of cases, but can be part of a multimodal approach for reducing arteriovenous malformation size prior to surgery or radiotherapy. Partial treatment of complex arteriovenous malformations may be more dangerous than no treatment. Protection devices can reduce complication rates in carotid artery stenting, but scientific evidence is still lacking. Until the results of comparative trials are available, carotid artery stenting is indicated only in selected patients. Angioplasty and stenting of intracranial arterosclerotic disease is feasible but remains a high-risk procedure, indicated only in highly selected patients. In acute stroke therapy, new thrombolytics and clot-retrieval devices may result in better recanalization rates. SUMMARY: Advances in endovascular therapy have occurred in all areas of cerebrovascular disease. To obtain maximal patient benefit, endovascular treatment should be performed as an interdisciplinary approach in high-volume centers. Importantly, long-term follow-up review is necessary to clarify the overall role of endovascular treatment in the management of cerebrovascular disease.     

Effects of nCPAP treatment over reaction time and sleepiness levels during vigilance

Several studies have shown that sleep fragmentation not only increases daytime sleepiness, but also deteriorates reaction time. Obstructive sleep apnea syndrome (OSAS) is characterized by interruptions in normal sleep patterns. Nasal Continuous Positive Airway Pressure (nCPAP) is the most frequently used treatment for OSAS. The objective of this investigation was to evaluate changes in daytime sleepiness levels and reaction time in apnea patients after nCPAP treatments of 1 and 3 months. The sample was composed of 51 obstructive sleep apnea patients (47 men and 4 women) with ages ranging between 30 and 65 years of age. Sleep apnea was diagnosed with a cardiorespiratory polygraph of the total hours of sleep. The Epworth Sleepiness Scale was used to assess daytime sleepiness. A BASIC software program was used to measure the simple perceptual reaction times in milliseconds. The results indicated statistically significant decreases in daytime sleepiness levels at 1 month (p < .000) and at 3 months (p < .000) of treatment. The results also showed statistically significant decreases in reaction times at one month (p < .000), as well as at 3 months (p < .000) of treatment. Results indicate an improvement in the vigilance levels of obstructive sleep apnea patients after 1 month and 3 months of nCPAP treatment.     

A clinical study and the national service framework for diabetes

Clinical assessment and management for anyone who has diabetes may be influenced by the development of the National Service Framework (NSF) for Diabetes. Through a case study, this article explains how the NSF for Diabetes and other recent NHS documentation has influenced our approach to managing a type 2 diabetic patient whose feet are categorised as 'high risk'. Some of the potential shortfalls of the NSF for Diabetes are also discussed in this context.     

Treatment of ataxia in cortical cerebellar atrophy with the GABAergic drug gabapentin. A preliminary study

The aim of this work was to investigate the efficacy of the GABAergic drug gabapentin in the treatment of the cerebellar signs caused by cortical cerebellar atrophy (CCA). Ten patients with CCA received gabapentin in single doses of 400 mg in an open-label study; thereafter, daily administration of 900-1,600 mg of gabapentin was continued during at least 4 weeks. An ataxia scale based on clinical findings was used to evaluate the cerebellar signs at baseline and after administration of the drug. A statistically significant improvement of the ataxia scores was found after single doses of 400 mg of gabapentin and after the administration of 900-1,600 mg of this drug during 4 weeks, as compared to the results obtained at baseline. An important clinical amelioration was also evident. Gabapentin has been demonstrated to be capable of improving the cerebellar signs in cases of CCA, after single doses and after continued administration of the drug during 4 weeks. GABAergic enhancement or supplementation could play an important role in the treatment of diseases of the cerebellar cortex associated with a deficit of GABA.